J INVASIVE CARDIOL 2009;21:e122–e125 Cardiac sources of cerebral emboli account for approximately 20% of all strokes. Atrial fibrillation1 and valvular heart2 disease represent the most common etiologies, however, paradoxical emboli complicating intracardiac defects is frequently investigated in young patients with cryptogenic strokes. Transthoracic (TTE) and transesophageal echocardiographic (TEE) assessment are recommended in such cases, with a focus on excluding the presence of left atrial appendage thrombus, patent foramen ovale or other intracardiac sources of emboli.3 Other less commonly recognized sources of paradoxical emboli include pulmonary arteriovenous malformations4 and persistent left-sided superior vena cava (PLSVC)-to left atrial connections.5 We describe successful percutaneous closure of a PLSVC which drained directly into the left atrium in a young patient with cryptogenic stroke. Case Report. A 38-year-old right-handed male experienced sudden onset of expressive aphasia along with right-sided hemiparesis while driving his car. The previous day, he had sustained minor left arm bruising while playing ice hockey. There was no antecedent history of prior cerebral ischemia, migraine, cardiac disease or arrhythmia. This episode was not accompanied by a headache or visual changes. His only cardiac risk factor was hyperlipidemia. On presentation, the patient was in sinus rhythm, with no evidence of cyanosis or clubbing. On neurological examination, he had mild right facial droop, subtle right arm weakness and expressive aphasia. His resting oxygen saturation was 92% by pulse oximetry. Magnetic resonance imaging (MRI) showed an area of infarction in the left middle cerebral artery territory. Venous Doppler ultrasonography of both lower limbs was normal. Doppler ultrasound of the extracranial carotid arteries and computed tomographic angiography (CTA) excluded significant atherosclerotic disease. Thrombophillia screening was within normal limits. TEE demonstrated a PLSVC draining into the left atrium. The coronary sinus was not dilated and not unroofed. Injection of agitated saline into the left antecubital vein first opacified the left atrial appendage and then the left atrium directly. Agitated saline injection into the right antecubital vein showed normal opacification of the right heart, with no right-to-left shunting. Cardiac MRI confirmed the presence of a PLSVC draining into the left atrium, with the left internal jugular and the left subclavian veins draining into the PLSVC. There was no bridging vein between the left- and right-sided vena cava (Figure 1). Given the cryptogenic nature of the stroke and the possibility of paradoxical embolism accounting for the event, closure of the PLSVC was recommended. The patient underwent cardiac catheterization with a view to therapeutic occlusion. An 8 Fr sheath was inserted into the left internal jugular vein. The patient’s PLSVC saturation was 80%, right upper pulmonary vein was 80%, left atrial saturation was 93% and hemoglobin was 15.7 g/dL. As no pulmonary artery or right superior vena cava (RSVC) saturations were measured, QpQs was not calculated. Angiography using an 8 Fr Gensini catheter confirmed the entry of the LSVC to the left atrium (Figure 2). On initial angiography of the left internal jugular vein, no collateral vessels were seen between the PLSVC and the RSVC (Figure 2A). A 0.035 inch extra-stiff Amplatzer wire was passed through the PLSVC and positioned across the mitral valve into the left ventricular apex. A test occlusion with a 34 mm AGA sizing balloon (AGA Corp., Plymouth, Minnesota) was then performed for 15 minutes and an increase in the mean pressure of the PLSVC from 6–11 mmHg was noted proximal to the balloon. A number of collateral vessels from the left neck filling the right SVC that had not been noted prior to test occlusion were observed (Figure 2B). A hemiazygous vein was also seen to be draining into the PLSVC. A 12 Fr AGA sheath was exchanged over the 0.035 inch extra-stiff Amplatzer exchange wire. We then selected a 20 mm post-MI ventricular septal defect occluder based on the largest diameter of the residual waist on the sizing balloon (17 mm). We ensured that the device was positioned distal to the site of the entrance of the hemiazygous vein. After device deployment, we verified the PLSVC pressure. Repeat angiography revealed complete occlusion of the segment (Figure 3) and the device was released without complications. The patient was discharged the next day on clopidogrel and aspirin. At follow up 6 months later, there were no features of recurrent cerebral emboli and no clinical evidence of venous hypertension. Discussion Embryology of PLSVC and anatomic variants. The thoracic embryonic venous system is composed of two pairs of large veins: the left and right superior cardinal veins, which return blood from cranial aspect of embryo, and the left and right inferior cardinal veins, which return blood from the caudal aspect. The right and left superior and inferior cardinal veins form common cardinal veins before entering the heart.6 The left common cardinal vein persists to form the coronary sinus.8 During the eighth week of gestation, an anastamosis forms between the right and left superior cardinal veins, resulting in the brachiocephalic vein. The portion of superior cardinal veins cephalic to the innominate vein form the internal jugular veins. The caudal portion on the right forms the RSVC, while it regresses on the left to become the ligament of Marshall.7 A PLSVC is a congenital malformation that is the result of failure of the normal regression of the left superior cardinal vein. The most common subtype of PLSVC results in the presence of both a left and right superior vena cava. A bridging innominate vein exists in about 60% of cases.8 In rare cases, the caudal right superior cardinal vein regresses, leading to an absent RSVC, with the PLSVC returning all the blood from the cranial aspect of the body. In 80–90% of individuals, a PLSVC drains into the right atrium via the coronary sinus and is of no hemodynamic consequence. In the remaining cases, it may drain directly into the inferior caval vein, the hepatic veins or into the left atrium through an unroofed coronary sinus,9 or as in this case, directly into the left atrium, resulting in a right-to-left-sided shunt.8 Clinical implications of PLSVC. A PLSVC, first recognized in 1738,10 has an estimated prevalence in the general population of 0.1–0.3%. Up to 10% of patients with a PLSVC can have a variety of associated structural anomalies including a bicuspid aortic valve, atrial septal defect, coronary sinus ostial atresia, cor triatriatum or coarctation of aorta.9 A PLSVC has been reported in up to one-fifth of patients with tetralogy of Fallot, and one-twelfth of patients with Eisenmenger’s syndrome.11 PLSVC has also been associated with electrophysiological abnormalities effecting the sinus node and conduction tissues. It is often recognized incidentally when the left cephalic or subclavian approach is used for central venous access or device therapy such as pacemaker implantation. To our knowledge, this is the first reported case of PLSVC as a cause of stroke. The likely mechanism is embolization (via the PLSVC to the left atrium) of thrombus formed as a consequence of trauma to the left arm. This same case has also been reported with an emphasis on echocardiographic features of diagnosis in this condition.12 Other reported indications for closure of a PLSVC draining into the left atrium include hypoxemia and paradoxical embolism. In such cases, surgical management may be indicated. Operative management includes creation of an intra-atrial baffle to connect the abnormal vein with the right atrium, or simple ligation of the PLSVC.13 Although these procedures have a low mortality rate, a sternotomy and associated morbidity can be anticipated, and could be avoided by percutaneous closure. Percutaneous closure of PLSVC. Before proceeding to percutaneous closure, several important anatomical aspects merit further discussion. Firstly, demonstration of collaterals from the PLSVC to the RSVC is a crucial preliminary step prior to proceeding with consideration of percutaneous closure. Demonstrating connections between the PLSVC and RSVC can be difficult with noninvasive imaging. The surgical literature suggests that if the connections from the PLSVC and RSVC are not apparent, a trial period of occlusion will usually indicate whether venous hypertension will be of clinical significance.11 Percutaneous balloon test occlusion can assist the interventionist in the catheterization laboratory as a useful means of detecting unrecognized collateral vessels and excluding an elevation in the mean venous pressure. Although we noted an increase in the mean pressure in the PLSVC from 6–11 mmHg, we felt this was not clinically significant and was likely to fall with time as collaterals are recruited. Despite the absence of collateral vessels on MRI, evidence of collaterals from the PLSVC to the RSVC on balloon occlusion angiography suggested the patient would be unlikely to develop clinical evidence of LSVC obstruction after device occlusion. Although there is no evidence in the literature to suggest an appropriate criterion for hemodynamic evaluation before and during test occlusion, we propose that an absolute pressure of 15 mmHg on test occlusion in adults is a reasonable cutoff above which clinically significant venous hypertension may occur. There have been several other reports of closure of PLSVC by percutaneous methods. Percutaneous occlusion of PLSVC has been reported in 2 adolescents with late cyanosis post Fontan procedure.14 In 1 case, a PLSVC draining into the coronary sinus, which communicated freely with the left atrium through an atrial septectomy, was closed using a 10–12 Amplatzer Duct Occluder. The second case was that of a patient with a PLSVC to the left atrial roof, which was not ligated at the time of surgery.14 In a patient with worsening dyspnea, Kougias et al described positioning of coils in a covered stent placed in the proximal innominate vein and the contiguous part of the PLSVC.15 This stent was intentionally restricted in its mid portion with the use of sutures prepared ex vivo for the purpose of “trapping” the coils. We do not favor this approach, as it is unnecessarily complicated, requiring multiple steps both before and during percutaneous intervention. Troost reported closure of a PLSVC draining into the left atrium in a patient with a frontal cerebral abscess using an Amplatzer ASD occluder.5 Both reports were able to confirm the presence of collaterals to the RSVC post procedure with angiograms. We believe documentation of collaterals from the PLSVC to the RSVC is an important step that should be performed before attempting definitive percutaneous repair. Another anatomic feature that is important to note is that PLSVC usually receives the hemiazygous vein before penetrating the pericardium and entering the heart.11 It is important to look for the hemiazygous vein and place the closure device distal to the hemiazygous connection so that any residual right-to-left shunting from the left-sided abdominal organs can be avoided. Finally, we chose a PI-VSD occluder — in preference to the standard muscular VSD occluder — as the PI-VSD occluder has a larger disc diameter relative to the waist. By oversizing the device (20 mm device in a 17 mm residual waist), we ensured adequate occlusion of the distensible venous structure and effective anchoring of the device. This minimized the risk of distal embolization into the left heart chambers. Another appropriate device that was not available at the time of this procedure would be the Amplatzer Vascular Plug II with a range in diameter from 3–22 mm. Once expanded, the 360-degree of vessel wall apposition creates a secure fit in the target vessel. Conclusion Exclusion of cardiac sources of systemic emboli remains an important element of management of patients with cryptogenic stroke. While identification of intracardiac defects such as patent foramen ovale is crucial, additional sources of paradoxical emboli such as pulmonary AV malformations and persistent left-sided SVC should also be sought. Percutaneous closure of a PLSVC can be safely achieved using presently available implants. Recognition of the potential anatomical variants in this population, awareness of the need for appropriate collateral flow, including the role of test occlusion, and the implications of device occlusion in terms of venous drainage of upper and lower body organs are essential. Acknowledgement. We wish to acknowledge the contributions of Dr. Nicholas Collins for his constructive comments and review of the final manuscript. From the *Toronto Congenital Cardiac Centre for Adults, Peter Munk Cardiac Centre, Toronto General Hospital/University Health Network, 200 Elizabeth Street, Toronto, and the §Department of Pediatrics, Division of Cardiology, Hospital for Sick Children, The University of Toronto School of Medicine, Toronto, Ontario, Canada. The authors report no conflicts of interest regarding the content herein. Manuscript submitted December 22, 2008, provisional acceptance given April 3, 2009 and final version accepted April 7, 2009. Address for correspondence: E.M. Horlick MDCM, FRCPC, Toronto Congenital Cardiac Centre for Adults, Peter Munk Cardiac Centre, Toronto General Hospital/University Health Network, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4. E-mail: firstname.lastname@example.org
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